# ent

id: cord-010328-uxpedpz8
type: CELL_LINE
entity:
  United States population Official CDC Health Advisory Distributed via the CDC Health Alert Network HAN Outbreak of Hepatitis A Virus HAV Infections among Persons Who Use Drugs and Persons Experiencing Homelessness Measles antibody


id: cord-018142-xt71w4nr
type: GGP
entity:
  ticlopidine clopidogrel cyclosporine A tacrolimus interferon alpha oral contraceptives quinine cisplatin mitomycin C bleomycin arsenic penicillamine D Ticlopidine


id: cord-018142-xt71w4nr
type: CHEMICAL
entity:
  tacrolimus interferon alpha oral contraceptives quinine cisplatin mitomycin C bleomycin arsenic penicillamine D Ticlopidine


id: cord-262776-6k7tcgfs
type: ORG
entity:
  Animal Health Report of the Federation of European Laboratory Animal Science Associations FELASA Working Group


id: cord-018845-r88bhiac
type: PROTEIN
entity:
  Trennung von Zellen und Plasma damit letzteres zur Bewahrung der Gerinnungsaktivität rasch eingefroren werden konnte Die


id: cord-018845-r88bhiac
type: PROTEIN
entity:
  Diese Reaktionen mit der Erbsubstanz hemmen deren Replikationsfähigkeit Für Frischplasma kommen schon lange Solvent Detergent SD Verfahren unter


id: cord-018845-r88bhiac
type: PROTEIN
entity:
  einer Energiedosis von 25 Thrombozytapheresekonzentrate sollten 2 4 10 11 Thrombozyten und höchstens 3 10 9 Erythrozyten


id: cord-018845-r88bhiac
type: PROTEIN
entity:
  unklar ob bei größeren Transfusionsvolumina die Additivlösung entfernt werden soll Für intrauterine Transfusionen muss die Additivlösung weitgehend entfernt werden damit der empfohlene Hämatokritwert von 75 85 eingestellt werden kann Hämatokrit von Erythrozytenkonzentraten


id: cord-018845-r88bhiac
type: GGP
entity:
  Spender nicht stärker belastet als jede Einzelspendeart Das maximale Bruttoentnahmevolumen soll 750 ml einschließlich Antikoagulans zuzüglich Untersuchungsproben nicht überschreiten An Spender


id: cord-018845-r88bhiac
type: CHEMICAL
entity:
  diastolischen Wert eingestellt werden Für einen ungehinderten Blutfluss wird der Blutbehälter unterhalb


id: cord-018845-r88bhiac
type: CHEMICAL
entity:
  N medianus und N ulnaris lokale Wundinfektionen und oder Thrombophlebitiden und Kompartmentsyndrome des Arms durch Einblutungen


id: cord-018845-r88bhiac
type: CHEMICAL
entity:
  bis heute zur Anwendung kommen Neben dem Weichmacher DEHP Di 2ethylhexyl phthalat wird auch TEHTM Tri


id: cord-018845-r88bhiac
type: CHEMICAL
entity:
  Transplantierte Patienten vor autologer Blutstammzellentnahme Patienten mit angeborenen Immundefekten sowie Feten


id: cord-305074-wz17u4e7
type: PROTEIN
entity:
  proinflammatory cytokines tumor necrosis factor TNF alpha interleukin IL 1 IL 2 IL 6 IL 17 granulocyte colony stimulating factor granulocyte macrophage colony stimulating factor


id: cord-305074-wz17u4e7
type: PROTEIN
entity:
  chemokines monocyte chemoattractant protein 1 macrophage inflammatory protein 1 alpha IL 8 interferon gamma


id: cord-335316-x2t5h5gu
type: ORG
entity:
  aguesia anosmia fatigue myalgia headache co morbidities respiratory cardiovascular renal diabetes autoimmune


id: cord-324908-ptlpsnfo
type: CELL_LINE
entity:
  ChiCTR2000030690 ChiCTR2000030627 ChiCTR2000030557 ChiCTR2000030381 ChiCTR2000030312 ChiCTR2000030046 ChiCTR2000030039 ChiCTR2000029850


id: cord-284208-8fsqgkw5
type: CELL_TYPE
entity:
  tumor bearing mouse plasma i e haptoglobin proteosome subunits fetuin B 14 3 3 zeta and MAGE B4 antigen


id: cord-266147-s8rxzm0t
type: LAW
entity:
  1 Contribution and Interpretation of Studies Validating the Inactivation and Removal of Viruses revised Inactivation


id: cord-304616-k92fa15l
type: EVENT
entity:
  International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Prevalence


id: cord-322714-s0wge7o4
type: ORG
entity:
  the National Healthcare Safety Network Biovigilance Component Hemovigilance Module Surveillance Protocol


id: cord-328352-l1q4uvxl
type: GGP
entity:
  Parkinson s disease 17 but such a pathological link being merely coincidental has been debated 18 Similarly the potential long term consequences of COVID 19


id: cord-321697-yua3apfi
type: WORK_OF_ART
entity:
  Stroke in the 21st century a snapshot of the burden epidemiology and quality of life Investigation of ischemic and demyelinating lesions


id: cord-006860-a3b8hyyr
type: PROTEIN
entity:
  fibdnogen Fbg yon Willebrand factor vWF homocystein Hcy C reactive protein CRP Thrombin generation markers


id: cord-006860-a3b8hyyr
type: PROTEIN
entity:
  anti TNFct monoclonal antibodies C Salat 1 P Boekstegers 2 E Holler 1 3 B Reinhardt I R Pihusch 1 K Werdan 2 M Kaul 4 T Beinert 2 E Hiller 1 Med Klinik III 1 und I 2 Klinikum Grosshadern der Ludwig Maximilians Universitat MOnchen H


id: cord-006860-a3b8hyyr
type: CELL_LINE
entity:
  human umbilical vein endothelial cell cultures K Fragiadaki C Salat R Pihusch B Reinhardt M Penovici E Hiller Med Klinik III Klinikum Grosshadern der Ludwig Maximilians Universitat MOnchen An


id: cord-006860-a3b8hyyr
type: PROTEIN
entity:
  PAt antigen 1 000 0 851 whole PAl antigen 0 851 1 000 t PA activity 0 594 0 492 bPA antigen 0 604 0 497 body mass index 0 502 0 462 triglycerides 0 452 0 441 total cholesterol 0 252 0 255 LDL cholesterol 0 263 0 264 HDL cholesterol 0 357 0 355 apolipoprotein B 0 428 0 402 apolipoprotein A I 0 233 0 211


id: cord-006860-a3b8hyyr
type: DNA
entity:
  HEREDITARY FACTOR X DEFECT GLA 25 LYS Huhmann I HOller B Krinninger B Turecek Pi Richter G Scharrer I Forberg E Watzke H Univ Klinik ftlr Innere Medi Abteilung for H matoiogie und Hamostaseologie W en Immuno Ag Wien Klinikum der J W Goethe Univ Frankfurt am Main Abt f Angiologie Factor X FX


id: cord-006860-a3b8hyyr
type: PROTEIN
entity:
  fibdnolytic factors plasminogen antiplasmin plasminogen activator inhibitor tissue plasminogen activator


id: cord-006860-a3b8hyyr
type: CELL_LINE
entity:
  Fix Perm Whenever cell surface positivity for a specific marker coincides with intracellular presence blocking of the surface


id: cord-006860-a3b8hyyr
type: CELL_LINE
entity:
  CTAD Vacutainer tubes 0 109 M Na citrate theophylline adenosine dipyridamole Patients with CAD showed significantly increased plasma concentrations of CD 62p HS 98 20 versus


id: cord-006860-a3b8hyyr
type: PROTEIN
entity:
  thrombin antithrombin III complex fiAT fibrinogen fiG D dimers DD cc2 antiplasmin tz2A prothrombin fragment 1 2 Fl 2


id: cord-006860-a3b8hyyr
type: GGP
entity:
  antibiotics 0 1 8 0 mg was added Then we defined the tlbrinolytlc activity of the mixes using azofibrin lysis and fhrombin activity was determined according to the speed of fibrin clots


id: cord-006860-a3b8hyyr
type: GGP
entity:
  HCC 85 8 9 10 11 12 13 14 15 16 17 2 78 5 12 0 253 8 24 1 35 2 3 4 8 14 9 menopause 90 3 97 6 87 4 41 4 307 05 57 6 39 8 9 10 0 12 6 HCC hormonal


id: cord-006860-a3b8hyyr
type: EVENT
entity:
  PROTEIN C RESISTANCE AND PLASMINOGEN DEFICIENCY IN A FAMILY WITH THROMBOPHILIA M Zttger 1 F Demarmels Biasiutti 1 Ch Mannhalter 2


id: cord-006860-a3b8hyyr
type: WORK_OF_ART
entity:
  A COMPARISON OF THE TECHNICAL PRINCIPLE OF THE roTEG COAGULATION ANALYSER AND CONVENTIONAL THROMBELASTOGRAPHIC SYSTEMS


id: cord-006860-a3b8hyyr
type: ORG
entity:
  U G6bel Department for Pediatric Hematology and Oncology Heinrich Heine University Medical Center Diisseldoff


id: cord-006860-a3b8hyyr
type: ORG
entity:
  Benjamin Franklin Free University of Berlin Dept of Medicine and Dept of Surgery Heinrich Heine University Dusseldod


id: cord-031907-ilhr3iu5
type: CELL_LINE
entity:
  healthy donors CytoTune iPS 2 0 Sendai Reprogramming Kit Protocol Clementino Fraga Filho UH 38583914 7 0000 5257 933 018 The EV


id: cord-031907-ilhr3iu5
type: PROTEIN
entity:
  e Phosphoglycerate Kinase 1 PGK1 Glyceraldehye 3 phosphate dehydrogenase GAPDH Aldolase ALDOA and Lactate dehydrogenase A LDHA


id: cord-031907-ilhr3iu5
type: PROTEIN
entity:
  adipocytes CD81 CD9 CD29 CD63 CD8 CD4 CD68 CD14 CD56 CD15 CD19 CD235a CD41a CD34 CD31 HLA ABC HLA G HLA DRDPDQ CD90 CD73 CD105 M Cadherin RYR1 RYR2 FABP4 DLK1


id: cord-031907-ilhr3iu5
type: PROTEIN
entity:
  tumour associated membrane receptors epidermal growth factor receptor EGFR receptor tyrosineprotein kinase ERBB2 Her2


id: cord-031907-ilhr3iu5
type: CELL_TYPE
entity:
  T cells CD4 CD8 CD25 Neutrophils GR 1 LY 6 C Dendritic cells CD11 c Macrophages CD11b MHCI MHCII NK cells CD27


id: cord-031907-ilhr3iu5
type: GGP
entity:
  Alzheimer s disease AD likely due to a progressive loss of hippocampal neurogenesis and escalation of neuroinflammation These changes are also accompanied by increased deposition of amyloid plaques


id: cord-031907-ilhr3iu5
type: GGP
entity:
  ADP p 0 01 and lower concentrations of PEVs and LEVs p 0 05 Furthermore thrombus formation was delayed p 0 003 and thrombus size was decreased p 0 008 on prostanoids Epoprostenol


id: cord-031907-ilhr3iu5
type: GGP
entity:
  Calon c Éric Boilard f and Francesca Cicchetti b a Centre de Recherche du CHU de Québec and Faculté de médecine Département de psychiatrie neurosciences Département de microbiologie infectiologie et d immunologie Evidences on microalgal extracellular vesicles


id: cord-031907-ilhr3iu5
type: PERSON
entity:
  Absara Hassan b Sonali Sharma b Jennifer Kwong b Montaha Rahman b Salma Adam b Jasmine Lee b Alvaro Villarreal Ponce


id: cord-031907-ilhr3iu5
type: ORG
entity:
  University of Pennsylvania Philadelphia USA b University of Pennsylvania philadelphia USA c Department of Bioengineering University of Pennsylvania Philadelphia USA Introduction Traumatic


id: cord-031907-ilhr3iu5
type: ORG
entity:
  Thomas Jefferson University Philadelphia USA b University of Pennsylvania School of Veterinary Medicine Philadelphia USA Introduction


id: cord-031907-ilhr3iu5
type: ORG
entity:
  Ikuhiko Nakase Department of Biological Science Graduate School of Science Osaka Prefecture University Sakai


id: cord-031907-ilhr3iu5
type: ORG
entity:
  the California Institute of Regenerative Medicine and National Institutes of Health Introduction Besides


id: cord-031907-ilhr3iu5
type: ORG
entity:
  a Laboratory of Clinical Investigation National Institutes of Ageing Baltimore USA b Department of Neurology


id: cord-031907-ilhr3iu5
type: ORG
entity:
  a Icahn School of Medicine at Mount Sinai New York USA b Mount Sinai Hospital New York USA c Department of Genetics and Genomic Sciences Department of Pathology Icahn School of Medicine Mount Sinai New York USA Introduction Diagnosis


id: cord-031907-ilhr3iu5
type: ORG
entity:
  The Brady Urological Institute Johns Hopkins University School of Medicine Baltimore USA Introduction One


id: cord-031907-ilhr3iu5
type: ORG
entity:
  a Vivex Biologics Inc Miami USA b VIVEX Biologics Inc Miami USA c VIVEX Biologics Inc Miami USA Introduction


id: cord-031907-ilhr3iu5
type: ORG
entity:
  Funding National University of Singapore R221000114114 National Medical Research Council Singapore R221000123213 Immunomodulatory


id: cord-031907-ilhr3iu5
type: ORG
entity:
  Integrative Physiology University of Nebraska Medical Center Omaha USA b Department of Cellular and Integrative Physiology University of Nebraska Medical Center Omaha USA Introduction miRNAs


id: cord-031907-ilhr3iu5
type: ORG
entity:
  the National Competitiveness and Excellence Program Catalan Institution for Research and Advanced Studies


id: cord-031907-ilhr3iu5
type: LAW
entity:
  PS08 Separation and Concentration a Laboratory of Clinical Biophysics Faculty of Health Sciences PS10 Diverse EV Biomarkers Chair Pia Siljander Faculty of Biological and Environmental Sciences Urinary


id: cord-031907-ilhr3iu5
type: ORG
entity:
  Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development


id: cord-031907-ilhr3iu5
type: CHEMICAL
entity:
  phenyl R 1 3 3 4 dimethoxyphenyl 2 6 dimethylimidazo 1 2 b pyridazin 8 yl pyrrolidin 3 yl carbamate PDDC


# bib

id: cord-006192-bqwchhwk
title: Plasma exudation and asthma
author: Persson, Carl G. A.
date: 1988
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100194/
doi: 10.1007/bf02714025
abstract:
  Several pieces of evidence support the view that exudation of plasma into the airway wall and into the airway lumen occurs in asthma. Vascular leakage of plasma results from inflammatory mediator-induced separation of endothelial cells in postcapillary venules belonging to the tracheobronchial circulation. Whereas proposed mediators of asthma induce reversible leakage, several antiasthma drugs exhibit antileakage effects in animals and humans. Potential consequences of plasma exudation are many. Mucosal/submucosal edema might contribute to airway hyperresponsiveness. Plasma exudate in the airway lumen in asthma may contribute to sloughing of epithelium, impairment of mucociliary transport, narrowing of small airways, and mucus plug formation. Exuded plasma may cause airway inflammation and constriction because of its content of powerful mediators, and chemoattractant factors and plasma proteins may condition the inflammatory cells abundant in asthmatic airways to release mediators in response to stimuli that otherwise would be innocuous to the cells. It is concluded that inflammatory stimulus-induced increase in macromolecular permeability of the tracheobronchial microvasculature and mucosa may be a significant pathogenetic mechanism in asthma and that the postcapillary venular endothelium and airway epithelium that regulate leakage of plasma are important effector cells in this disease.


id: cord-006860-a3b8hyyr
title: 40th Annual Meeting of the GTH (Gesellschaft für Thrombose- und Hämostaseforschung)
author: nan
date: 1996
txt: ./txt/cord-006860-a3b8hyyr.txt
cache: ./cache/cord-006860-a3b8hyyr.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103196/
doi: 10.1007/bf00641048
abstract: nan
summary:
  Dept of Pediatrics, University Hospitals Kiel and Mtinster, Germany Resistance to activated protein C (APCR), in the majority of cases associated with the Arg 506 Gin point mutation in the factor V gene is present in more than 50 % of patients < 60 years of age with unexplained thrombophilia. The regular APC resistance test is not applicable to plasma from Orally anticoagulated (OAC) or heparinized patients due to decreased levels of vitamin K-dependent clotting factors and to thrombin inhibition by antithrombin, respectively. On admission an extensive coagulation screen yielded the following results (n/normal, t/elevated, I/reduced, +/positive, -/negative): PT t, aPTT t, Tr n, factor II, V, VIII n, factor VII, IX, XI, XII /,, fibrinogan t, ATIII n, protein C, S *, activated protein C sensitivity ratio 1.92 ($), FV-Leidenmutation PCR -, fibrinolytic system n, TAT t, Ft÷2 t, lupus anticoagulant +, heparin induced platelet antibodies +; no diagnosis of a specific autoimmuna disorder could be made.


id: cord-010328-uxpedpz8
author: Ciencewicki, Jonathan M.
date: 2020-04-22
txt: ./txt/cord-010328-uxpedpz8.txt
cache: ./cache/cord-010328-uxpedpz8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176631/
doi: 10.1038/s41598-020-63794-y
summary:
  In this study, source plasma from donation centers in various locations of the Southwestern quarter of the United States was surveyed for antibody titers to hepatitis A virus (HAV), measles virus (MeV), and cytomegalovirus (CMV). Safety measures implemented nearly two decades ago-collaborative, industry-wide epidemiological surveillance of the donor population, judicious selection of donors, rigorous testing of plasma by serological and molecular (e.g., nucleic acid testing) methods and validation of manufacturing methods for virus clearance capacity-provide a high degree of confidence that IG products, regardless of plasma origin, safely deliver a diverse, natural combination of human polyclonal antibodies 1,2 . The analyses of individual units originating from select pools served to demonstrate that a number of centers in the US Southwest are capable of consistently generating plasma with elevated anti-HAV Ig titers.

title:
  Plasma Donors in the Southwestern United States Positively Contribute to the Diverse Therapeutic Antibody Profile of Immune Globulin Products

abstract:
  Human-plasma-derived immune globulin (IG) is used in augmentation therapy to provide protective levels of antibodies to patients with primary immune deficiency diseases (PIDD) and for prophylaxis against infectious diseases. To maintain the breadth of antibodies necessary for clinical protection, it is important to understand regional patterns of antibody seroprevalence in source plasma from which IG products are manufactured. In this study, source plasma from donation centers in various locations of the Southwestern quarter of the United States was surveyed for antibody titers to hepatitis A virus (HAV), measles virus (MeV), and cytomegalovirus (CMV). A broad range of anti-HAV Ig plasma titers was observed among these centers, with some centers exhibiting 3–5 times the titers of the others. Minor to no differences were observed for levels of anti-MeV and anti-CMV, respectively. Importantly, elevated anti-HAV Ig titers were broadly observed across plasma units obtained from the centers exhibiting high titers, indicative of a potential regional phenomenon among donors as opposed to few donors with singularly high titers. Plasma from these high-titer centers conferred significantly greater neutralization against HAV in vitro. The outcomes of this study give a glimpse of the antibody diversity inherent in human plasma used to manufacture IG products..


id: cord-018142-xt71w4nr
title: Thrombotic Microangiopathy Syndrome in the ICU
author: Samy Modeliar, S.
date: 2006
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122943/
doi: 10.1007/3-540-33396-7_20
abstract:
  Major studies designed to improve our understanding of the pathophysiology of TMA have been conducted over recent years. This improved knowledge opens up new perspectives for more targeted treatment. However, until these innovative treatments become available, early diagnosis of these diseases is essential in order to rapidly initiate specific treatment, as the interval between diagnosis and initiation of plasma exchange is a decisive element in the prognosis of TTP. Treatment must not be stopped too early or too rapidly and must take into account the various associated factors, especially the presence of infection.


id: cord-018492-d34tyar7
title: Dried Plasma
author: Zaza, Mouayyad
date: 2019-05-06
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123378/
doi: 10.1007/978-3-030-20820-2_8
abstract:
  Dried plasma provides an alternative for early plasma transfusion in the resuscitation of hemorrhagic shock in environments where fresh frozen plasma is not immediately available. It is produced by freeze-drying or spray-drying liquid or thawed plasma. It is shelf-stable for prolonged periods, can be stored at room temperature, and is easy to transport, reconstitute, and administer. It was widely used in WWII but fell out of favor due to the risk of infectious disease transmission. The German and French experiences with lyophilized plasma are the most extensive and show a good track record of efficacy and safety. Recent studies show many beneficial effects of dried plasma in the treatment of shock in large animal models. Currently, no FDA-licensed product is available in the USA, but several are under development.


id: cord-018845-r88bhiac
title: Gewinnung, Herstellung und Lagerung von Blut und Blutkomponenten
author: Sachs, U. J. H.
date: 2010-11-21
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123830/
doi: 10.1007/978-3-642-12765-6_16
abstract:
  Blutspender leisten einen wertvollen Dienst für die Gemeinschaft: Die ständige Verfügbarkeit von Blutkomponenten ist zur unverzichtbaren Voraussetzung für viele Bereiche der Medizin geworden. Nicht nur die Gewinnung und Aufarbeitung von Blut und Blutbestandteilen zur Sicherstellung einer qualitativ wie quantitativ guten Versorgung, sondern auch die kompetente Betreuung der Spender ist eine der großen Aufgaben der Transfusionsmedizin.


id: cord-031907-ilhr3iu5
title: ISEV2020 Abstract Book
author: nan
date: 2020-07-15
txt: ./txt/cord-031907-ilhr3iu5.txt
cache: ./cache/cord-031907-ilhr3iu5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480431/
doi: 10.1080/20013078.2020.1784511
abstract: nan
summary:
  L.M., and the National Institutes of Health (R35GM119623) to T.R.G. The addition of a size exclusion chromatography step to various urinary extracellular vesicle concentrating methods reveals differences in the small RNA profile Introduction: Urinary extracellular vesicles (EVs) and their RNA cargo are a novel source of biomarkers for various diseases, however non-vesicular RNA (e.g. associated with proteins) is also present within urine. We then evaluated efficiency of heart targeting for eAAV9 or eAAV6 and standard AAV9 or AAV6 encoding for EGFP, mCherry or firefly luciferase in different human cell lines in vitro, in black mouse and in passive immunity nude mouse model in vivo using flow cytometry, confocal microscopy, Langendorff perfusion system and Methods: HLHS patients (n = 3) after Glenn procedure and swine (n = 3) after PAB were given RV injections of allogeneic/xenogeneic MSCs. Donor-specific, HLA-I+, exosomes were isolated from plasma.


id: cord-261653-0vtghtp7
title: Recruitment Strategy for Potential COVID-19 Convalescent Plasma Donors
author: Andersen, Kylie J.
date: 2020-09-21
txt: ./txt/cord-261653-0vtghtp7.txt
cache: ./cache/cord-261653-0vtghtp7.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0025619620310557
doi: 10.1016/j.mayocp.2020.09.021
abstract: nan
summary:
  Thus, the present narrative overviews the strategy developed by our team to identify and recruit COVID-19 survivors to donate convalescent plasma at the Mayo Clinic Blood Donor Center in Rochester, Minnesota. Rochester, Minnesota required a strategy to interface with the community of recovering COVID-19 patients and recruit eligible convalescent plasma donors. Overall, this recruitment strategy utilized a simple survey, an algorithm for triaging donors, a workflow for connecting donors with Mayo Clinic Blood Donor Center, a team of physician navigators (including medical students) to screen eligible donors, and a support center for donor questions. Our web-based recruitment survey and all e-mail communications to interested potential donors contained the e-mail address for our convalescent plasma service center. The service center team used available resources from the US FDA, Mayo Clinic, and the blood banking community to support questions regarding donor eligibility and COVID-19 testing.


id: cord-262776-6k7tcgfs
title: Assessment of the viral safety of antivenoms fractionated from equine plasma
author: Burnouf, Thierry
date: 2004-09-30
url: https://www.sciencedirect.com/science/article/pii/S1045105604000223
doi: 10.1016/j.biologicals.2004.07.001
abstract:
  Abstract Antivenoms are preparations of intact or fragmented (F(ab′)2 or Fab) immunoglobulin G (IgG) used in human medicine to treat the severe envenomings resulting from the bites and stings of various animals, such as snakes, spiders, scorpions, or marine animals, or from the contact with poisonous plants. They are obtained by fractionating plasma collected from immunized horses or, less frequently, sheep. Manufacturing processes usually include pepsin digestion at acid pH, papain digestion, ammonium sulphate precipitation, caprylic acid precipitation, heat coagulation and/or chromatography. Most production processes do not have deliberately introduced viral inactivation or removal treatments, but antivenoms have never been found to transmit viruses to humans. Nevertheless, the recent examples of zoonotic diseases highlight the need to perform a careful assessment of the viral safety of antivenoms. This paper reviews the characteristics of equine viruses of antivenoms and discusses the potential of some manufacturing steps to avoid risks of viral contamination. Analysis of production parameters indicate that acid pH treatments and caprylic acid precipitations, which have been validated for the manufacture of some human IgG products, appear to provide the best potential for viral inactivation of antivenoms. As many manufacturers of antivenoms located in developing countries lack the resources to conduct formal viral validation studies, it is hoped that this review will help in the scientific understanding of the viral safety factors of antivenoms, in the controlled implementation of the manufacturing steps with expected impact on viral safety, and in the overall reinforcement of good manufacturing practices of these essential therapeutic products.


id: cord-266147-s8rxzm0t
title: Modern Plasma Fractionation
author: Burnouf, Thierry
date: 2007-03-28
url: https://www.sciencedirect.com/science/article/pii/S0887796306000940
doi: 10.1016/j.tmrv.2006.11.001
abstract:
  Protein products fractionated from human plasma are an essential class of therapeutics used, often as the only available option, in the prevention, management, and treatment of life-threatening conditions resulting from trauma, congenital deficiencies, immunologic disorders, or infections. Modern plasma product production technology remains largely based on the ethanol fractionation process, but much has evolved in the last few years to improve product purity, to enhance the recovery of immunoglobulin G, and to isolate new plasma proteins, such as α1-protease inhibitor, von Willebrand factor, and protein C. Because of the human origin of the starting material and the pooling of 10 000 to 50 000 donations required for industrial processing, the major risk associated to plasma products is the transmission of blood-borne infectious agents. A complete set of measures—and, most particularly, the use of dedicated viral inactivation and removal treatments—has been implemented throughout the production chain of fractionated plasma products over the last 20 years to ensure optimal safety, in particular, and not exclusively, against HIV, hepatitis B virus, and hepatitis C virus. In this review, we summarize the practices of the modern plasma fractionation industry from the collection of the raw plasma material to the industrial manufacture of fractionated products. We describe the quality requirements of plasma for fractionation and the various treatments applied for the inactivation and removal of blood-borne infectious agents and provide examples of methods used for the purification of the various classes of plasma protein therapies. We also highlight aspects of the good manufacturing practices and the regulatory environment that govern the whole chain of production. In a regulated and professional environment, fractionated plasma products manufactured by modern processes are certainly among the lowest-risk therapeutic biological products in use today.


id: cord-271764-um001ffd
author: Garraud, Olivier
date: 2020-06-27
url: https://www.sciencedirect.com/science/article/pii/S1473050220301634?v=s5
doi: 10.1016/j.transci.2020.102858
abstract: nan
title:
  Passive immunotherapy with convalescent plasma against COVID-19? What about the evidence base and clinical trials?


id: cord-274150-ukdha3ap
title: Convalescent Plasma Therapy for Coronavirus Disease 2019
author: Choi, Jun Yong
date: 2020-09-03
txt: ./txt/cord-274150-ukdha3ap.txt
cache: ./cache/cord-274150-ukdha3ap.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32989938/
doi: 10.3947/ic.2020.52.3.307
summary:
  Given its rapid acquisition, convalescent plasma therapy has been considered as an emergency intervention in several pandemics, including the Spanish flu, severe acute respiratory syndrome coronavirus (SARS-CoV-1), and West Nile virus, and more recently, Ebola virus [7] [8] [9] . Although large-scale randomized controlled trials have not yet been performed, and most studies did not evaluate neutralizing activities of used convalescent plasma, previous experiences on convalescent plasma therapy for the treatment of emerging infectious diseases provide us with important historical precedents that this intervention might be useful for confronting the COVID-19 epidemics. To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID19 , an open-label, multicenter, randomized clinical trial was performed in seven medical centers in Wuhan, China. Some patients who recover from viral diseases may not have high titers of neutralizing antibodies, which are crucial for the effectiveness of convalescent plasma therapy [13, 14] .

abstract:
  Convalescent plasma has been used for decades to prevent and treat a wide range of infectious diseases for which no specific treatment is available. The use of convalescent plasma involves transfusing plasma collected from patients who have recovered from a viral illness, in an attempt to transfer virus-neutralizing antibodies and confer passive immunity. In addition to the antiviral mechanisms of neutralizing antibodies, the immunomodulatory effects of plasma components could have benefits. Several small and large-scale studies have shown the effects of convalescent plasma for the treatment of severe coronavirus disease 2019 (COVID-19). In addition to transfusion-related side effects, unexpected side effects such as antibody-dependent enhancement (ADE) may occur during convalescent plasma therapy, but early safety studies have not found any cases of ADE among more than 5,000 participants. With historical precedents and recent clinical studies, convalescent plasma therapy should be considered as a candidate therapy for COVID-19 given the limited effectiveness of antiviral drugs and lack of a vaccine. A system to secure safe collection and use of convalescent plasma should be developed as a response to the pandemic. Further clinical trials should be conducted to determine the safety and efficacy of convalescent plasma therapy concurrently with its clinical use.


id: cord-277811-j58qvyum
author: Mehrani, Hossein
date: 2011-01-07
url: https://www.ncbi.nlm.nih.gov/pubmed/21906349/
doi: 10.1186/1559-0275-8-2
title:
  Plasma proteomic profile of sulfur mustard exposed lung diseases patients using 2-dimensional gel electrophoresis

abstract:
  INTRODUCTION: Sulfur mustard "bis (2-chlroethyl) sulphide" (SM) is a chemical warfare agent that remains a threat to human health. The aim of this study was to identify protein expression signature or biomarkers that reflect chronic lung damages induced by SM exposure. METHODS: Prior to analysis, plasma was fractionated using ethanol precipitation. Using two dimensional SDS-PAGE; fractionated protein profiles of 20 healthy and 20 exposed patients with lung diseases were established. Selected protein spots were successfully identified with MALDI TOF MS/MS. RESULTS: The results show that α1 haptoglobin isoforms were detected in plasma of the all lung disease patients but none of the healthy controls. Amyloid A1 isoforms was also detected in plasma of the lung disease patients but none of the healthy controls. Moreover, low molecular weight proteins were enriched in ethanol supernatant compared to ethanol precipitate. CONCLUSION: Our present results and previous studies suggest that ongoing tissue remodeling is involved in SM exposed lung damage patients. These finding might improve patient care and suitable therapies.


id: cord-282252-07uzz649
title: Convalescent Plasma Therapy: A Passive Therapy for An Aggressive COVID‐19
author: Sahu, Kamal Kant
date: 2020-05-21
txt: ./txt/cord-282252-07uzz649.txt
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extension: .txt
mime: text/plain
url: https://doi.org/10.1002/jmv.26047
doi: 10.1002/jmv.26047
summary:
  The basic concept for use of convalescent plasma in COVID-19 is as a delivery system for viral neutralizing antibodies, that is to confer passive immunity. Considering the aforementioned limitations and the potential risks, appropriate triage systems should be utilized; hence, plasma therapy use is currently restricted only to critically ill patients. The FDA recommends two clinical indications for the current usage of convalescent plasma therapy in COVID-19 patients(12) Scenario A (Severe disease) which is defined as one or more of the following: On April 3, 2020, the FDA cleared the path for the use of this potential lifesaving therapy under any of the following three routes[1] enrollment in a clinical trial, [2] via the national expanded access treatment protocol, and [3] under a single patient emergency investigational new drug application (eIND). Lacking a vaccine and with limited antiviral options against SARS-CoV-2, this is an ideal time to try convalescent plasma therapy in COVID-19 patients. Treatment of 5 Critically Ill Patients with COVID-19 with Convalescent Plasma Effectiveness of convalescent plasma therapy in severe COVID-19 patients

abstract:
  As of May 19, 2020, there are in total 4,986,200 laboratory‐confirmed Coronavirus disease‐2019 (COVID‐19) cases. 2% (45,425) out of 2,657,390 active COVID‐19 cases are critically ill and might be requiring intensive care support.(1,2) Unfortunately, even after six months since its first detection, we still do not have any definitive treatment options for COVID‐19 pneumonia. This article is protected by copyright. All rights reserved.


id: cord-284208-8fsqgkw5
author: Zolla, Lello
date: 2008-11-07
url: https://doi.org/10.1016/j.drudis.2008.09.013
doi: 10.1016/j.drudis.2008.09.013
title:
  Proteomics studies reveal important information on small molecule therapeutics: a case study on plasma proteins

abstract:
  The most abundant proteins in serum, such as albumin and IgG, act as molecular sponges that bind and transport low molecular weight proteins/peptides and drugs. In the near future, pharmacoproteomics, the use of proteomic technologies in the field of drug discovery and development, and interactomics, the branch of proteomics which is concerned with identifying interactions between proteins, will allow researchers to (i) know the specific protein changes that occur in biological compartments in response to drug administration; (ii) design small novel therapeutic molecules that can have extended half-lives if carried by plasma protein in the blood stream. Advances in these fields will open new avenues of tailor-made molecular therapy, reducing present limitations on treatment arising from toxicity and inefficiency. In this short review we report and discuss the most recent developments arising from the use of proteomic tools in blood plasma protein research, looking at the identification of proteins found in plasma as well as their interactions with small molecules such as drugs, peptides, organic chemicals and metals. We believe this research demonstrates that proteomic technologies, and in particular pharmacoproteomics, interactomics and post-translational modification analysis, could be instrumental in the design of new tailor-made drugs leading to substantial improvements in molecular therapy.


id: cord-284582-xwedgllw
title: Cell-free DNA in plasma as an essential immune system regulator
author: Korabecna, M.
date: 2020-10-15
url: https://doi.org/10.1038/s41598-020-74288-2
doi: 10.1038/s41598-020-74288-2
abstract:
  The cell-free DNA (cfDNA) is always present in plasma, and it is biomarker of growing interest in prenatal diagnostics as well as in oncology and transplantology for therapy efficiency monitoring. But does this cfDNA have a physiological role? Here we show that cfDNA presence and clearance in plasma of healthy individuals plays an indispensable role in immune system regulation. We exposed THP1 cells to healthy individuals’ plasma with (NP) and without (TP) cfDNA. In cells treated with NP, we found elevated expression of genes whose products maintain immune system homeostasis. Exposure of cells to TP triggered an innate immune response (IIR), documented particularly by elevated expression of pro-inflammatory interleukin 8. The results of mass spectrometry showed a higher abundance of proteins associated with IIR activation due to the regulation of complement cascade in cells cultivated with TP. These expression profiles provide evidence that the presence of cfDNA and its clearance in plasma of healthy individuals regulate fundamental mechanisms of the inflammation process and tissue homeostasis. The detailed understanding how neutrophil extracellular traps and their naturally occurring degradation products affect the performance of immune system is of crucial interest for future medical applications.


id: cord-294585-dl5v9p50
title: Pathogen‐reduction methods: advantages and limits
author: Klein, H. G.
date: 2009-02-13
txt: ./txt/cord-294585-dl5v9p50.txt
cache: ./cache/cord-294585-dl5v9p50.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32328162/
doi: 10.1111/j.1751-2824.2009.01224.x
summary:
  However, because blood contains numerous labile proteins and fragile cells, and because there is a wide array of potentially infectious agents, no single method of pathogen-inactivation will likely preserve all blood components, yet effectively remove all viruses, bacteria, spores, protozoa and prions. Riboflavin/ultraviolet light treatment has been evaluated in preclinical studies and found to result in reduction of infectivity by many pathogens including west Nile virus, intracellular HIV, bacteria and protozoa. Therapeutic efficacy and safety of platelets treated with a photochemical process for pathogen inactivation: the SPRINT Trial Clinical safety of platelets photochemically treated with amotosalen HCl and ultraviolet A light for pathogen inactivation: the SPRINT trial Fresh frozen plasma prepared with amotosalen HCl (S-59) photochemical pathogen inactivation: transfusion of patients with congenital coagulation factor deficiencies Therapeutic efficacy and safety of red blood cells treated with a chemical process (S-303) for pathogen inactivation: a Phase III clinical trial in cardiac surgery patients

abstract:
  Pathogen‐reduction (inactivation) provides a proactive approach to reducing transfusion‐transmitted infection. Pathogen‐reduction technologies have been successfully implemented by plasma fractionators resulting in no transmission of human immunodeficiency, hepatitis C, or hepatitis B viruses by US‐licensed plasma derivatives since 1987. Fractionation technologies cannot be used to treat cellular blood components. Although blood donor screening, deferral and disease testing have drastically reduced the incidence of transfusion‐transmitted diseases, the threat of new or re‐emerging pathogens remains. Of particular concern is the silent emergence of a new agent with a prolonged latent period in which asymptomatic infected carriers would donate and spread infection. The ultimate goal of pathogen‐inactivation is to reduce transmission of potential pathogens without significantly compromising the therapeutic efficacy of the cellular and protein constituents of blood. The acceptable technology must not introduce toxicities into the blood supply nor result in neoantigen formation and subsequent antibody production. Several promising pathogen‐inactivation technologies are being developed and tested, and others are currently in use, but all of them have limits. Pathogen‐reduction promises an additional ‘layer of protection’ from infectious agents and has the potential to impact the safety of blood transfusions worldwide.


id: cord-294684-wfsdjs1f
author: Vesnaver, Elisabeth
date: 2020-11-02
url: https://www.ncbi.nlm.nih.gov/pubmed/33138828/
doi: 10.1186/s12961-020-00643-4
title:
  Barriers and enablers to source plasma donation by gay, bisexual and other men who have sex with men under revised eligibility criteria: protocol for a multiple stakeholder feasibility study

abstract:
  BACKGROUND: Blood donation policy in Canada for gay, bisexual and other men who have had sex with men (gbMSM) has changed progressively in the last decade from indefinite deferral to 3-month deferral from last male-to-male sex. Driven by safety data and overseen by the national regulator, more inclusive policies continue to redress the disparity in donation for gbMSM. At the same time, the need for source plasma to prepare fractionated blood products is growing worldwide. The collection and processing of source plasma ensures greater safety compared to whole blood donation with respect to transfusion-transmitted infection. This greater safety offers an opportunity to evolve policies for gbMSM from time-based to behaviour-based deferral using revised eligibility criteria. However, changing policies does not in itself necessarily guarantee that gbMSM will donate or that staff in donor clinics are ready to support them to do so. In anticipation of a move to behaviour-based donation screening for gbMSM in Canada, we aim to assess the acceptability of and perceived barriers and enablers to source plasma donation using revised screening criteria for gbMSM among key stakeholders to inform policy implementation strategies. METHODS: This mixed-methods feasibility study will involve gbMSM and donor centre staff to understand modifiable barriers to implementing more inclusive eligibility criteria. Key informant interviews and surveys will be rooted in the Theoretical Domains Framework to identify modifiable factors associated with source plasma donation motives in gbMSM and training needs in donation centre staff. We will use an integrated knowledge translation approach involving a partnership between researchers, the national blood operator and gbMSM, situating knowledge users as key research team members to ensure their perspectives inform all aspects of the research. DISCUSSION: Our integrated knowledge translation approach will provide a more comprehensive and collaborative understanding of blood operator and gbMSM needs while accelerating the implementation of study findings. Given the historical backdrop of the decades of exclusion of sexually active gbMSM from blood donation, this study has the potential not only to inform a process and policy for gbMSM to donate source plasma, a blood product, but also offers opportunities for new relationships between these knowledge users.


id: cord-304616-k92fa15l
author: Izes, Aaron M.
date: 2020-08-05
url: https://doi.org/10.1371/journal.pone.0236754
doi: 10.1371/journal.pone.0236754
title:
  Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats

abstract:
  The antimalarial agent mefloquine is currently being investigated for its potential to inhibit feline coronavirus and feline calicivirus infections. A simple, high pressure liquid chromatography assay was developed to detect mefloquine plasma concentrations in feline plasma. The assay’s lower limit of quantification was 250 ng/mL. The mean ± standard deviation intra- and inter-day precision expressed as coefficients of variation were 6.83 ± 1.75 and 5.33 ± 1.37%, respectively, whereas intra- and inter-day accuracy expressed as a percentage of the bias were 11.40 ± 3.73 and 10.59 ± 3.88%, respectively. Accordingly, this validated assay should prove valuable for future in vivo clinical trials of mefloquine as an antiviral agent against feline coronavirus and feline calicivirus. However, the proportion of mefloquine binding to feline plasma proteins has not been reported. The proportion of drug bound to plasma protein binding is an important concept when developing drug dosing regimens. As cats with feline infectious peritonitis (FIP) demonstrate altered concentrations of plasma proteins, the proportion of mefloquine binding to plasma proteins in both clinically normal cats and FIP-affected cats was also investigated. An in vitro method using rapid equilibrium dialysis demonstrated that mefloquine was highly plasma protein bound in both populations (on average > 99%).


id: cord-305074-wz17u4e7
author: Fernandez, Javier
date: 2020-08-24
url: https://www.ncbi.nlm.nih.gov/pubmed/32833695/
doi: 10.1097/ccm.0000000000004613
title:
  Plasma Exchange: An Effective Rescue Therapy in Critically Ill Patients With Coronavirus Disease 2019 Infection

abstract:
  Infection by severe acute respiratory syndrome coronavirus-2 can induce uncontrolled systemic inflammation and multiple organ failure. The aim of this study was to evaluate if plasma exchange, through the removal of circulating mediators, can be used as rescue therapy in these patients. DESIGN: Single center case series. SETTING: Local study. SUBJECTS: Four critically ill adults with coronavirus disease 19 pneumonia that failed conventional interventions. INTERVENTIONS: Plasma exchange. Two to six sessions (1.2 plasma volumes). Human albumin (5%) was used as the main replacement fluid. Fresh frozen plasma and immunoglobulins were administered after each session to avoid coagulopathy and hypogammaglobulinemia. MEASUREMENTS AND MAIN RESULTS: Serum markers of inflammation and macrophage activation. All patients showed a dramatic reduction in inflammatory markers, including the main cytokines, and improved severity scores after plasma exchange. All survived to ICU admission. CONCLUSIONS: Plasma exchange mitigates cytokine storm, reverses organ failure, and could improve survival in critically ill patients with coronavirus disease 2019 infection.


id: cord-305130-vz72ldbo
author: Keil, Shawn D.
date: 2020-05-14
url: https://doi.org/10.1111/vox.12937
doi: 10.1111/vox.12937
title:
  Inactivation of severe acute respiratory syndrome coronavirus 2 in plasma and platelet products using a riboflavin and ultraviolet light‐based photochemical treatment

abstract:
  BACKGROUND AND OBJECTIVE: Severe acute respiratory distress syndrome coronavirus‐2 (SARS‐CoV‐2), the causative agent of coronavirus disease 2019 (COVID‐19), is a member of the coronavirus family. Coronavirus infections in humans are typically associated with respiratory illnesses; however, viral RNA has been isolated in serum from infected patients. Coronaviruses have been identified as a potential low‐risk threat to blood safety. The Mirasol Pathogen Reduction Technology (PRT) System utilizes riboflavin and ultraviolet (UV) light to render blood‐borne pathogens noninfectious, while maintaining blood product quality. Here, we report on the efficacy of riboflavin and UV light against the pandemic virus SARS‐CoV‐2 when tested in both plasma and platelets units. MATERIALS AND METHODS: Stock SARS‐CoV‐2 was grown in Vero cells and inoculated into either plasma or platelet units. Those units were then treated with riboflavin and UV light. The infectious titres of SARS‐CoV‐2 were determined by plaque assay using Vero cells. A total of five (n = 5) plasma and three (n = 3) platelet products were evaluated in this study. RESULTS: In both experiments, the measured titre of SARS‐CoV‐2 was below the limit of detection following treatment with riboflavin and UV light. The mean log reductions in the viral titres were ≥3·40 and ≥4·53 for the plasma units and platelet units, respectively. CONCLUSION: Riboflavin and UV light effectively reduced the titre of SARS‐CoV‐2 in both plasma and platelet products to below the limit of detection in tissue culture. The data suggest that the process would be effective in reducing the theoretical risk of transfusion transmitted SARS‐CoV‐2.


id: cord-319013-oytqcifa
title: Convalescent Plasma Therapy for COVID-19: State of the Art
author: Focosi, Daniele
date: 2020-08-12
txt: ./txt/cord-319013-oytqcifa.txt
cache: ./cache/cord-319013-oytqcifa.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32792417/
doi: 10.1128/cmr.00072-20
summary:
  In the first retrospective, randomized controlled trial published to date, 39 patients in New York with severe COVID-19 were transfused with 2 units of ABO-type matched CP with anti-Spike antibody titers of Ն1:320 (measured by a two-step Spike proteindirected ELISA). CP (9 to 13 ml/kg from donors with S-RBD IgG titer of Ն1:640) was associated with a negative SARS-CoV-2 PCR test at 72 h in 87.2% of the CP group versus 37.5% of the BSC group, but clinical improvement at 28 days was statistically different only in patients with severe, but not in life-threatening, disease (104) . Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol Anti-SARS-CoV-2 virus antibody levels in convalescent plasma of six donors who have recovered from COVID-19

abstract:
  Convalescent plasma (CP) therapy has been used since the early 1900s to treat emerging infectious diseases; its efficacy was later associated with the evidence that polyclonal neutralizing antibodies can reduce the duration of viremia. Recent large outbreaks of viral diseases for which effective antivirals or vaccines are still lacking has renewed the interest in CP as a life-saving treatment. The ongoing COVID-19 pandemic has led to the scaling up of CP therapy to unprecedented levels. Compared with historical usage, pathogen reduction technologies have now added an extra layer of safety to the use of CP, and new manufacturing approaches are being explored. This review summarizes historical settings of application, with a focus on betacoronaviruses, and surveys current approaches for donor selection and CP collection, pooling technologies, pathogen inactivation systems, and banking of CP. We additionally list the ongoing registered clinical trials for CP throughout the world and discuss the trial results published thus far.


id: cord-321697-yua3apfi
title: Cell-free nucleic acid patterns in disease prediction and monitoring—hype or hope?
author: Crigna, Adriana Torres
date: 2020-10-29
txt: ./txt/cord-321697-yua3apfi.txt
cache: ./cache/cord-321697-yua3apfi.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s13167-020-00226-x
doi: 10.1007/s13167-020-00226-x
summary:
  This article highlights the involvement of circulating CFNAs in local and systemic processes dealing with the question, whether specific patterns of CFNAs in blood, their detection, quantity and quality (such as their methylation status) might be instrumental to predict a disease development/progression and could be further utilised for accompanying diagnostics, targeted prevention, creation of individualised therapy algorithms, therapy monitoring and prognosis. Especially severe, prolonged and/ or chronic stress of any origin such as exercise-induced oxidative stress [22] (see "Physical activity and exercise-induced oxidative stress" section), hormonal stress [23] , emotional stress and psychological burden [24] [25] [26] [27] as well as metabolic stress, e.g. in diabetes mellitus [28, 29] (see also below "Association between diabetes mellitus and carcinogenesis: diagnostic and therapeutic potential of cell-free nucleic acids" section) and hyperhomocysteinaemia [30, 31] amongst others, is associated with highly increased ROS production and insufficient repair capacity-both linked to oxidative damage of mitochondria and consequent mitochondrial dysfunction leading to the development of cardiovascular impairments [32] [33] [34] , neuro/degenerative pathologies [34] [35] [36] [37] , impaired healing [34] and malignant cell transformation [34, [38] [39] [40] [41] [42] .

abstract:
  Interest in the use of cell-free nucleic acids (CFNAs) as clinical non-invasive biomarker panels for prediction and prevention of multiple diseases has greatly increased over the last decade. Indeed, circulating CFNAs are attributable to many physiological and pathological processes such as imbalanced stress conditions, physical activities, extensive apoptosis of different origin, systemic hypoxic-ischemic events and tumour progression, amongst others. This article highlights the involvement of circulating CFNAs in local and systemic processes dealing with the question, whether specific patterns of CFNAs in blood, their detection, quantity and quality (such as their methylation status) might be instrumental to predict a disease development/progression and could be further utilised for accompanying diagnostics, targeted prevention, creation of individualised therapy algorithms, therapy monitoring and prognosis. Presented considerations conform with principles of 3P medicine and serve for improving individual outcomes and cost efficacy of medical services provided to the population.


id: cord-322714-s0wge7o4
title: Safety Update: COVID-19 Convalescent Plasma in 20,000 Hospitalized Patients
author: Joyner, Michael J.
date: 2020-07-19
url: https://www.sciencedirect.com/science/article/pii/S0025619620306510?v=s5
doi: 10.1016/j.mayocp.2020.06.028
abstract:
  Abstract Objective To provide an update on key safety metrics after transfusion of convalescent plasma in hospitalized COVID-19 patients, having previously demonstrated safety in 5,000 hospitalized patients. Patients and Methods From April 3 to June 2, 2020, the US FDA Expanded Access Program for COVID-19 convalescent plasma transfused a convenience sample of 20,000 hospitalized patients with COVID-19 convalescent plasma. Results The incidence of all serious adverse events was low; these included transfusion reactions (n=89; <1%), thromboembolic or thrombotic events (n=87; <1%), and cardiac events (n=680, ∼3%). Notably, the vast majority of the thromboembolic or thrombotic events (n=55) and cardiac events (n=562) were judged to be unrelated to the plasma transfusion per se. The seven-day mortality rate was 8.6% (8.2%, 9.0%), and was higher among more critically-ill patients relative to less ill counterparts, including patients admitted to the intensive care unit vs. not admitted (10.5% vs. 6.0%), mechanically ventilated vs. not ventilated (12.1% vs. 6.2%), and with septic shock or multiple organ dysfunction/failure vs. those without dysfunction/failure (14.0% vs. 7.6%). Conclusion These updated data provide robust evidence that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19, and support the notion that earlier administration of plasma within the clinical course of COVID-19 is more likely to reduce mortality.


id: cord-324908-ptlpsnfo
title: Convalescent plasma: possible therapy for novel coronavirus disease 2019
author: Cao, Huiling
date: 2020-05-02
txt: ./txt/cord-324908-ptlpsnfo.txt
cache: ./cache/cord-324908-ptlpsnfo.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1111/trf.15797
doi: 10.1111/trf.15797
abstract: nan
summary:
  16 Public Health of England and the International Severe Acute Respiratory and Emerging Infection Consortium 17 put forward that convalescent plasma could be a promising specific treatment for serious Middle East respiratory syndrome (MERS), and further evaluation is needed in human clinical trials. Although many studies have reported the efficacy and safety of convalescent plasma infusion in the treatment of various infections, due to the lack of large-scale, randomized, well-designed, and prospective clinical trials, we tend to consider convalescent plasma as an "empirical" therapy. Mortality in the treatment group was significantly lower than in the nontreatment group ( controlled trial reported that patients who received immune plasma and standard care for severe influenza showed a nonsignificant reduction in the mortality rate. In conclusion, the transfusion of up to 500 mL of convalescent plasma with unknown levels of neutralizing antibodies in 84 patients with confirmed Ebola virus infection was not associated with a significant improvement in survival.


id: cord-326176-n0xo3e53
title: Multiple myeloma in 16 cats: a retrospective study
author: Patel, Reema T.
date: 2008-03-05
url: https://www.ncbi.nlm.nih.gov/pubmed/16270258/
doi: 10.1111/j.1939-165x.2005.tb00059.x
abstract:
  Background: There is limited published information regarding feline multiple myeloma. Diagnostic criteria are derived from canine studies and to our knowledge, have not been critically reviewed for cats. Objective: To evaluate the clinical and laboratory findings in cats with multiple myeloma and appraise diagnostic criteria. Methods: Retrospective evaluation of medical records was performed. Inclusion required an antemortem diagnosis of multiple myeloma using 2 of 4 criteria: 1) ≥20% plasma cells in the bone marrow, or ≥10% if atypical plasma cells; 2) paraproteinemia; 3) radiographically‐evident osteolysis; 4) light chain proteinuria. Alternatively, a postmortem diagnosis was based on the findings of multiple plasma cell neoplasms, with marrow involvement. Results: Sixteen cats were diagnosed with multiple myeloma between 1996 and 2004, with a median age of 14.0 years; 9 of 16 (56%) were castrated males, and 7 of 16 (44%) were spayed females. Laboratory abnormalities included hyperglobulinemia (14/16, 87.5%), with 11/14 (78.5%) monoclonal and 3/14 (21.4%) biclonal gammopathies; hypoalbuminemia (4/16, 25%); light chain proteinuria, (4/9, 44.4%); hypocholesterolemia (11/16, 68.7%); hypercalcemia, (3/15, 20%); nonregenerative anemia, (11/16, 68.7%); regenerative anemia, (1/16, 6.2%); neutropenia (5/15, 33.3%); thrombocytopenia (8/16, 50%); and marrow plasmacytosis (14/15, 93.3%). Plasma cells were markedly immature, atypical, or both in 10 of 12 (83.3%) cats. Focal or multifocal osteolysis was noted in 6 of 12 (50%) cats for which radiographs were available for review; generalized osteopenia was found in 1 (8.3%) cat. Noncutaneous, extramedullary tumors were found in all cats assessed, 7/7 (100%), including spleen (6), liver (3), and lymph nodes (4). The disease in 1 of 2 cats with cutaneous tumors progressed to plasmacytic leukemia. Conclusions: Common findings in feline multiple myeloma include atypical plasma cell morphology, hypocholesterolemia, anemia, bone lesions, and multi‐organ involvement. Based on the results of this study, we advocate modifying diagnostic criteria in cats to include consideration of plasma cell morphology and visceral organ infiltration.


id: cord-328352-l1q4uvxl
title: The Disillusioned Comfort with COVID-19 and the Potential of Convalescent Plasma and Cell Therapy
author: Borlongan, Mia C.
date: 2020-08-25
url: https://doi.org/10.1177/0963689720940719
doi: 10.1177/0963689720940719
abstract:
  Coronavirus disease 2019 or COVID-19 is highly infectious, which can lead to acute and chronic debilitating symptoms, as well as mortality. The advent of safe and effective vaccines or antiviral drugs remains distant in the future. Practical public health measures, such as social distancing, hand washing, and wearing a face mask, are the current recommended guidelines by the Centers for Disease Control and Prevention for limiting the spread of the virus. Weakened immune system and aberrant inflammation represent a major pathological symptom of COVID-19 patients. Based on the unique immunomodulatory properties of both convalescent plasma and stem cells, we discuss here their potential use for treating COVID-19.


id: cord-329228-yjvw2ee1
author: Shikata, N.
date: 2006-10-13
url: https://www.ncbi.nlm.nih.gov/pubmed/17031477/
doi: 10.1007/s00726-006-0412-0
title:
  Multi-layered network structure of amino acid (AA) metabolism characterized by each essential AA-deficient condition

abstract:
  The concentrations of free amino acids in plasma change coordinately and their profiles show distinctive features in various physiological conditions; however, their behavior can not always be explained by the conventional flow-based metabolic pathway network. In this study, we have revealed the interrelatedness of the plasma amino acids and inferred their network structure with threshold-test analysis and multilevel-digraph analysis methods using the plasma samples of rats which are fed diet deficient in single essential amino acid. In the inferred network, we could draw some interesting interrelations between plasma amino acids as follows: 1) Lysine is located at the top control level and has effects on almost all of the other plasma amino acids. 2) Threonine plays a role in a hub in the network, which has direct links to the most number of other amino acids. 3) Threonine and methionine are interrelated to each other and form a loop structure.


id: cord-335316-x2t5h5gu
author: Madariaga, M. L. L.
date: 2020-06-23
url: http://medrxiv.org/cgi/content/short/2020.06.21.20132944v1?rss=1
doi: 10.1101/2020.06.21.20132944
title:
  Clinical predictors of donor antibody titer and correlation with recipient antibody response in a COVID-19 convalescent plasma clinical trial

abstract:
  Background: Convalescent plasma therapy for COVID-19 relies on the transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. Methods: Multivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. Results: Mean symptom duration of plasma donors was 11.9 and 7.8% (8/103) had been hospitalized. Antibody titers ranged from 0 to 1:3,892 (anti-receptor binding domain (RBD)) and 0 to 1:3,289 (anti-spike). Multivariable analysis demonstrated that higher anti-RBD and anti-spike titer were associated with increased age, hospitalization for COVID-19, fever, and absence of myalgia (all p<0.05). Fatigue was significantly associated with anti-RBD (p=0.03) but not anti-spike antibody titer (p=0.11). In pairwise comparison among ABO blood types, AB donors had higher anti-RBD titer than O negative donors (p=0.048) and higher anti-spike titer than O negative (p=0.015) or O positive (p=0.037) donors. Eight of the ten recipients were discharged, one remains on ECMO and one died on ECMO. No toxicity was associated with plasma transfusion. After excluding two ECMO patients and adjusting for donor antibody titer, recipient anti-RBD antibody titer increased on average 31% per day during the first three days post-transfusion (p=0.01) and anti-spike antibody titer by 40.3% (p=0.02). Conclusion: Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titer to COVID-19. Despite variability in donor titer, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion among COVID-19 patients is needed to determine the clinical efficacy of this therapy.


id: cord-336177-p7b7yw28
author: Selvi, Valeria
date: 2020-09-22
url: https://doi.org/10.1155/2020/2606058
doi: 10.1155/2020/2606058
title:
  Convalescent Plasma: A Challenging Tool to Treat COVID-19 Patients—A Lesson from the Past and New Perspectives

abstract:
  On March 11(th), 2020, the World Health Organization declared COVID-19 infection as a pandemic. Since it is a novel virus, there are basically no proven drugs or therapies; although many laboratories in different countries are working to develop a vaccine, it will take time to make it available. Passive immunization is the therapy born from the intuition of Behring and Kisato in the late 19(th) century. It was widely used for the treatment of bacterial infections until the discovery of antibiotics, as well as during the viral pandemics of the 20(th) century and of the beginning of the 21(st); it still has clinical applications (e.g., tetanus prevention). This paper summarizes the basic principles of passive immunization, with particular reference to convalescent plasma. The literature concerning its use during past epidemics and the results of the first clinical studies concerning its use during the current pandemic are discussed too. A large section is dedicated to the analysis of the possible, although rare, side effects. Recently, in 2017, the WHO Blood Regulators Network (BRN) published a position paper, recommending convalescent plasma as the first-choice treatment to be tested in the absence of authorized drugs; however, this strategy has not been followed. In the current epidemic, the principle of passive immunization through convalescent plasma has been applied in several circumstances and particularly in patients with serious complications. The first reported results are encouraging and confirm the effectiveness of plasma therapy and its safety. Also, the FDA has proposed plasma treatment in order to face the increasingly complex situation and manage patients with serious or immediately life-threatening COVID-19 disease. Several studies and clinical programs are still ongoing.


id: cord-349031-tbof9yqi
title: Novel Antiviral Strategies in the Treatment of COVID-19: A Review
author: Chen, Shiu-Jau
date: 2020-08-20
url: https://doi.org/10.3390/microorganisms8091259
doi: 10.3390/microorganisms8091259
abstract:
  The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2), is still a global public health problem for humans. It has caused more than 10,000,000 infections and more than 500,000 deaths in the world so far. Many scientists have tried their best to discover safe and effective drugs for the treatment of this disease; however, there are still no approved standard therapeutics or effective antiviral drugs on the market. Many new drugs are being developed, and several traditional drugs that were originally indicated or proposed for other diseases are likely to be effective in treating COVID-19, but their safety and efficacy are controversial, under study, or in clinical trial phases. Fortunately, some novel antiviral strategies, such as convalescent plasma, clustered regularly interspaced short palindromic repeats (CRISPR), and mesenchymal stem cell (MSC) therapy, potentially offer an additional or alternative option or compassionate use for the people suffering from COVID-19, especially for critically ill patients, although their safety and efficacy are also under study. In this review, we explore the applications, possible mechanisms, and efficacy in successful cases using convalescent plasma, CRISPR, and MSC therapy for COVID-19 treatment, respectively. Furthermore, the perspectives and limitations of these novel antiviral strategies are evaluated.


id: cord-351328-ly72scru
title: Points to consider in the preparation and transfusion of COVID‐19 convalescent plasma
author: Epstein, Jay
date: 2020-05-14
url: https://doi.org/10.1111/vox.12939
doi: 10.1111/vox.12939
abstract:
  This document prepared and endorsed by the Working Party on Global Blood Safety of the International Society of Blood Transfusion presents elements, as of April 2020, to take into consideration in the preparation and transfusion of COVID-19 convalescent plasma as a possible treatment approach of COVID-19. The document covers the following important factors to have in mind when considering this treatment: (a) eligibility criteria of convalescent COVID-19 patients to donate whole blood or plasma, (b) pre-screening and pre-donation testing of convalescent COVID-19 donors; (c) criteria for collection of COVID-19 plasma; (d) post-donation treatment of plasma; and (e) it offers recommendations for plasma transfusion.


id: cord-352985-5ccrkfsa
author: Putter, Jeffrey S.
date: 2020-09-04
url: https://www.ncbi.nlm.nih.gov/pubmed/32948465/
doi: 10.1016/j.transci.2020.102934
title:
  An Update on COVID-19 Infection Control Measures, Plasma-Based Therapeutics, Corticosteroid Pharmacotherapy and Vaccine Research

abstract:
  This communication provides a compilation on aspects of COVID-19 infection control measures, describes the potential role of therapeutic plasma exchange to reduce fatality rates, addresses precautions concerning dexamethasone pharmacotherapy and updates the current status on the availability of vaccines. As part of passive immunotherapy, it focuses on various blood derivatives. These include coronavirus neutralising antibodies extracted from different sources to be administered as a pure hyper concentrate intramuscularly or for upgrading and standardising the specific potency of high affinity antibodies. These processes are intended to compose standardised pooled bioproducts of corona convalescent plasma/cryosupernatant that are pathogen inactivated for additional safety by well-established UV technologies. For the best practice of optimising plasma exchange, hyper concentrate NAb should be added to the cryosupernatant, which contains some of the active principles of corona convalescent plasma. The cryosupernatant apart from the high molecular weight viscous part of cold insoluble proteins that are removed, is equivalent to CCP, but makes it safer for general application. Such a bioproduct is often used routinely for substitution therapy of thrombotic thrombocytopenic purpura. Alternative resources of large-scale specific coronavirus antibodies warrant further exploration such as cadaveric donations. The early uses of therapeutic plasma exchange and low molecular weight heparin, for any clinical trial in development is warranted, in order to interdict the intense inflammatory/kinin driven cascade. Because coronavirus positive patients are highly prone to thrombosis, thromboprophylaxis is necessary, even some time after recovery guided by the laboratory data.


